Chronic Non-bacterial Osteomyelitis Treated With Pamidronate (CNOPAM)

Chronic Non-bacterial Osteomyelitis Treated With Pamidronate in a Randomised Placebo Controlled Trial

In a randomized double blind placebo controlled trial to investigate the effect of pamidronate in treatment of chronic non bacterial osteomyelitis.

Main objective:

1. Reduction of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.
2. Healing of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.

Secondary objectives:

1. Changes in bone lesions in whole body MRI between baseline and week 12 and between week 12 and week 36
2. Changes in bone lesions of anterior chest-wall (adults) evaluated by CT scan between baseline and week 36.
3. Changes in patient self reported outcome measures
4. Changes in inflammatory markers and bone markers.

Study Overview

• Status: Unknown
• Conditions: Musculoskeletal Disease; Immune System Disease
• Intervention / Treatment: Drug: Pamidronatdinatrium; Other: Natrium chloride 9mg/ml

Detailed Description

Chronic non-bacterial osteomyelitis is a multifocal inflammatory bone disorder. The pathogenesis is unknown. The disease is mainly diagnosed in childhood. There is a strong association with inflammatory disorders of the skin, mainly psoriasis. The disease is characterized by recurrent episodes of pain and disability. It is unclear if SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) might be the adult version of chronic non-bacterial osteomyelitis. The disease can persist in adulthood and course chronic bone deformations.

Wholebody MRI is the most sensitive imaging for diagnosing and monitoring the non bacterial osteitis.

The treatment of chronic non-bacterial osteomyelitis is largely empiric. First line treatment is NSAID (Non Steroidal Anti-Inflammatory Drug). When NSAID is inadequate the bisphosphonate pamidronate has been described relief pain in small cohorts in retrospective studies.

In this research protocol, investigators seek to investigate if it is beneficial to use pamidronate in the treatment of chronic non bacterial osteomyelitis and the osteitis component in SAPHO syndrome. Primary outcome is whole body MRI. Secondary outcome is CT scan, patient measure reported outcome and biomarkers. A biobank may help us to understand the pathogenesis and future treatment targets of chronic non bacterial osteomyelitis.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Caroline Marie Andreasen, MD; Phone Number: +45 7846 4252; Email: carand@rm.dk
• Study Contact Backup: Name: Ellen Margrethe Hauge, Professor; Phone Number: +45 7846 4252

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Universityhospital of Aarhus, Denmark
    • Contact: Caroline Marie Andreasen, MD; Phone Number: +4578464252; Email: carand@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 9-65 years (inclusive)

• Fulfilling the diagnostic criteria for chronic non bacterial osteomyelitis:

  1. Mono-, oligo- or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis)
  2. Diagnostic score according to A. Jansson criteria (2009) > 39 or malignancy and infection excluded by biopsy
  3. Symptoms > 6 weeks
• Volunteer, signed written informed content

Exclusion Criteria:

• Age older than 65 years
• Age younger than 9 years
• Pregnant women or nursing (breastfeeding) mothers
• Hypersensitivity to pamidronate, bisphosphonate og additives in pamidronate
• Known history or current lymphoproliferative disease
• History of surgery on glandula thyroidea
• Known alcohol/medical abuse
• Poor dental status
• Low Vitamin D- status
• Liver/ kidney disease
• Abnormal laboratory screening for comorbidity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pamidronatdinatrium 3mg/ml; Pamidronatdinatrium 1 mg/kg max 60 mg for 3 days every 3 month in total of 3 series (0,3,6 month). First day first series 0,5mg/kg max 30 mg.	Drug: Pamidronatdinatrium; Other Names: Pamidronat, Pamifos, Aredia
Placebo Comparator: Natrium chloride 9 mg/ml; Natrium chloride 9 mg/ml volume equals experimental drug	Other: Natrium chloride 9mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Wholebody MRI	Changes between baseline and week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CT scan of the anterior chestwall (adults)		Changes between baseline and week 36
Systemic inflammatory markers	TNF- α,IL-1 β, IL-8, IL-18, IL-17, INF-ƴ, IL-6, IL-10, IL-11, IL-21, MIP 1-alfa (CCL3, 22) and IL-1Ra	Changes between baseline and week 1, 4, 12, 24 and 36
Systemic bone markers	s-CTX og s-NTX, P1NP, C1NP, TRACP 5b, bone alkaline phosphatase	Changes between baseline and week 1, 4, 12, 24 and 36
Wholebody MRI		Changes between baseline and week 12 and changes between week 12 and 36
Changes in Health Assesment Questionnaire score		Changes between baseline and week 1, 4, 12, 24 and 36
Changes in Children Assesment Questionnaire score		Changes between baseline and week 1, 4, 12, 24 and 36
Changes in Visual Analog Score for pain		Changes between baseline and week 1, 4, 12, 24 and 36

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Caroline Marie Andreasen, MD, University hospital of Aarhus, Denmark

Publications and helpful links

General Publications

• Andreasen CM, Jurik AG, Deleuran BW, Horn HC, Folkmar TB, Herlin T, Hauge EM. Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, placebo-controlled pilot trial. Scand J Rheumatol. 2020 Jul;49(4):312-322. doi: 10.1080/03009742.2020.1724324. Epub 2020 Jun 2.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: November 2, 2015
• First Posted (Estimate): November 3, 2015

Study Record Updates

• Last Update Posted (Estimate): November 16, 2016
• Last Update Submitted That Met QC Criteria: November 15, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Pamidronate; SAPHO syndrome; Chronic non-bacterial osteomyelitis; Chronic recurrent multifocal osteomyelitis; Non- bacterial osteomyelitis; Whole body MRI; Inflammatory bone disease; Autoinflammatory disease
• Additional Relevant MeSH Terms: Infections; Bone Diseases; Bone Diseases, Infectious; Musculoskeletal Diseases; Immune System Diseases; Osteomyelitis
• Other Study ID Numbers: 48438